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We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.

Objective: Biomarkers for Alzheimer disease (AD) can detect the disease pathology in asymptomatic subjects and individuals with mild cognitive impairment (MCI), but their cognitive prognosis remains uncertain. We aimed to determine the prognostic value of b-amyloid imaging, alone and in combination with memory performance, hippocampal atrophy, and apolipoprotein E e4 status in nondemented, older individuals. Methods: A total of 183 healthy individuals (age 5 72.0 6 7.26 years) and 87 participants with MCI (age 5 73.7 6 8.27) in the Australian Imaging, Biomarkers, and Lifestyle study of ageing were studied. Clinical reclassification was performed after 3 years, blind to biomarker findings. b-Amyloid imaging was considered positive if the 11 C-Pittsburgh compound B cortical to reference ratio was 1.5. Results: Thirteen percent of healthy persons progressed (15 to MCI, 8 to dementia), and 59% of the MCI cohort progressed to probable AD. Multivariate analysis showed b-amyloid imaging as the single variable most strongly associated with progression. Of combinations, subtle memory impairment (Z score 5 20.5 to 21.5) with a positive amyloid scan was most strongly associated with progression in healthy individuals (odds ratio [OR] 5 16, 95% confidence interval [CI] 5 3.7-68; positive predictive value [PPV] 5 50%, 95% CI 5 19-81; negative predictive value [NPV] 5 94%, 95% CI 5 88-98). Almost all amnestic MCI subjects (Z score 21.5) with a positive amyloid scan developed AD (OR 5 1; PPV 5 86%, 95% CI 5 72-95; NPV 5 100%, 95% CI 5 80-100). Hippocampal atrophy and e4 status did not add further predictive value.View this article online at wileyonlinelibrary.com.